The thesis of this proposal is that prefrontal cortex is a critical anatomical substrate for working memory and, furthermore, that different regions of prefrontal cortex are critical for working memory in different information domains (spatial, object and verbal memory). Frontal lobe dysfunction in schizophrenia results in deficits in working memory which, in turn, underlie much of the symptomatology of the disease. Using magnetic resonance imaging (MRI), we propose to examine the neuroanatomical regions involved in different domains of working memory in humans. Our research plan encompasses three specific aims: (1) Use MR activation imaging to examine the differential activation of dorsolateral and lateral inferior regions of the prefrontal cortex during performance of spatial and object working memory tasks. Our prediction is that spatial memory tasks will increase blood flow in dorsolateral areas and object memory will activate lateral inferior regions. We will also compare the distribution of activated prefrontal regions in spatial and object memory tasks to verbal memory tasks constructed to share the same stimulus and response requirements. (2) Use MR activation imaging to examine the distributed network properties of working memory systems; for example, the posterior parietal cortex should be differentially activated in spatial memory functions; the inferotemporal regions in object memory functions; and the left posterior superior temporal gyrus in linguistic tasks. (3). Use MR activation imaging to examine hippocampal activation. Additional tasks in which novel visual and auditory stimulus pairs must be associated will be used to examine relative activation of hippocampus and prefrontal regions in associative memory tasks. The proposed research will also include the further development of MR activation imaging. This new technique shows great promise as an alternative modality for activation imaging with the potential for widespread application.